Human African trypanosomiasis (HAT), also known as sleeping sickness, is a vector-borne parasitic disease. The parasites concerned are protozoa belonging to the Trypanosoma genus, such as (Trypanosoma brucei rhodesiense (Tbr) or Trypanosoma brucei gambiense (Tbg). They are transmitted to humans by tsetse fly (Glossina genus) bites which have acquired their infection from human beings or from animals harbouring the human pathogenic parasites.
In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph. This is known as a haemolymphatic phase, which entails bouts of fever, headaches, joint pains and itching.
In the second stage the parasites cross the blood-brain barrier to infect the central nervous system. This is known as the neurological phase. In general this is when more obvious signs and symptoms of the disease appear: changes of behavior, confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is an important feature of the second stage of the disease. Without treatment, sleeping sickness is considered fatal.
Malaria is another one of most dangerous infectious diseases in tropical and subtropical countries, afflicting about 300 million people. The pathogen of the disease is a protozoan parasite, Plasmodium sp. which is transmitted by Anopheles mosquitoes. Four species of malaria parasites can infect humans under natural conditions: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. P. falciparum and P. vivax cause the most infections worldwide. P. falciparum is the agent of severe, potentially fatal malaria. Malaria caused by P. falciparum is responsible for nearly 1 million deaths annually. Based on recent estimates from the WHO, worldwide, there were an estimated 247 million malaria cases among 3.3 billion people at risk living in 109 countries. Infections caused by P. falciparum and P. vivax account for more than 90% of global malaria burden; the former being responsible for nearly all the deaths due to malaria, nearly a million deaths of children under 5 years.
Membrane activated chelators (MACs) are neuroprotective drugs that modulate cell membrane metal ion homeostasis by adopting an inactive conformation outside only in the lipid environment of cell membranes. In this environment, the drugs are able to unable to bind metal ions at their elevated non-physiological concentrations, which results in a drug with excellent tolerability. See, for example U.S. Pat. Nos. 6,458,837 and 7,799,831, incorporated by reference herein. DP-b99, a BAPTA-based lipophilic MAC of calcium, zinc and copper has been safely used in humans and is currently in phase III clinical trials for treatment of acute ischemic stroke. The safety, tolerability, and efficacy of related compounds DP-109 and DP-460 has also been demonstrated as these compounds have shown promise in mouse models of Alzheimer's disease and amyotrophic lateral sclerosis
There still exists a need for more effective chemotherapeutic treatments for parasitic diseases such as HAT and malaria, around the world.